Of the numerous biological agents that may be used as weapons, the Working Group on Civilian Biodefense has identified Bacillus anthracis as one of the most serious agents. The most effective defense against this agent on a broad scale is through an aggressive vaccination program. Currently, there is one vaccine for use in the United States for anthrax, produced by the BioPort Corporation in Lansing Michigan. This vaccine is a filtrate from cultures of an avirulent, nonencapsulated strain of Bacillus anthracis which produces the protective antigen (PA) and that is adsorbed to aluminum hydroxide (termed anthrax vaccine adsorbed or AVA). With recent events foreshadowing broader usage of the vaccine in the general population, a more palatable formulation is necessary, one that will be equally if not more effective than the current vaccine. It is our hypothesis that oral delivery of the anthrax antigen will induce a robust mucosal and systemic immune response against the bacteria by selective targeting of intact antigens to the distal ileum Peyer's patches. Further, an oral vaccine has the benefits of ease of administration, with the likelihood of reduced adverse effects. This proposal will test the hypothesis that a potent antigen delivered intact to the distal ileum will induce a potent immune response. This strategy is supported by recent immunologic data and made possible by TSRL's emerging pharmaceutic technology, the PORT System Capsule -an innovative capsule-based system capable of delivering one or more timed doses of a drug in a single dosage form. Our ultimate goal for the phase 1 portion of this project will be an oral formulation that will elicit an immune response comparable to that of the FDA approved product, AVA, in the dog model. We feel that development of this technology for oral vaccines will have an immediate impact in the area of anthrax vaccine and will also have utility for a wide variety of other vaccines.